Project 3: Specific Aim #1: To assess efficacy of endogenous cardiac stem cells in a porcine model of acute ischemic cardiomyopathy. We will use our established swine model of anterior wall Ml to determine whether endogenous cardiac stem cells (CSCs) beneficially affect left ventricular remodeling in the setting of post-Mi ventricular dysfunction. The results of this study will define the efficacy and safety of CSCs in repairing acute scar formation and define the most effective method of CSC delivery (intracoronary infusion vs. intramyocardial injection) and CSC dose (cell numbers) for our human studies (Aims #2 and #3). In Aim #2, we will assess the safety of autologous CSC therapy in patients with acute ischemic cardiomyopathy. This study will assess the safety of autologous CSC therapy in patients with a recent ST segment elevation myocardial infarction and resultant depressed left ventricular systolic function (EF<0.35) identified by MRI. Autologous CSCs will be harvested, propagated, and percutaneously implanted one month post-Mi and following automatic internal cardiodefibrillator (AICD) placement. Safety will be assessed by determining (a) clinical status; (b) arrhythmia potential (via Holter, AICD monitoring and interrogation, and EP study); and (c) LV function and infarct size over the 90 day follow up period. Aim #3: To assess efficacy of autologous CSC therapy in patients with acute ischemic cardiomyopathy. This randomized, placebo-controlled trial will determine the efficacy of CSC therapy in improving left ventricular function and remodeling and clinical status of patients with acute ischemic cardiomyopathy. Patients presenting with their first ST segment elevation Ml and left ventricular systolic dysfunction (EF<0.35) will be randomized to treatment with (a) autologous CSC or (b) placebo to be placed one month post-Mi and following AICD placement. Efficacy (improvement in left ventricular function and remodeling), clinical benefit, and safety will be assessed over the 6 month follow-up period.